title: Seamless vascularized large-diameter tubular collagen scaffolds reinforced with polymer knittings for esophageal regenerative medicine.
abstract: A clinical demand exists for alternatives to repair the esophagus in case of congenital defects, cancer, or trauma. A seamless biocompatible off-the-shelf large-diameter tubular scaffold, which is accessible for vascularization, could set the stage for regenerative medicine of the esophagus. The use of seamless scaffolds eliminates the error-prone tubularization step, which is necessary when emanating from flat scaffolds. In this study, we developed and characterized three different types of seamless tubular scaffolds, and evaluated in vivo tissue compatibility, including vascularization by omental wrapping. Scaffolds (luminal Ø ∼ 1.5 cm) were constructed using freezing, lyophilizing, and cross-linking techniques and included (1) single-layered porous collagen scaffold, (2) dual-layered (porous+dense) collagen scaffold, and (3) hybrid scaffold (collagen+incorporated polycaprolacton knitting). The latter had an ultimate tensile strength comparable to a porcine esophagus. To induce rapid vascularization, scaffolds were implanted in the omentum of sheep using a wrapping technique. After 6 weeks of biocompatibility, vascularization, calcification, and hypoxia were evaluated using immunohistochemistry. Scaffolds were biocompatible, and cellular influx and ingrowth of blood vessels were observed throughout the whole scaffold. No calcification was observed, and slight hypoxic conditions were detected only in the direct vicinity of the polymer knitting. It is concluded that seamless large-diameter tubular collagen-based scaffolds can be constructed and vascularized in vivo. Such scaffolds provide novel tools for esophageal reconstruction.
authors.affiliation: 1 Department of Biochemistry 280, RIMLS, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Henk R
authors.initials: HR
authors.lastname: Hoogenkamp
authors.forename: Martin J W
authors.initials: MJ
authors.lastname: Koens
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Geutjes
authors.forename: Herwig
authors.initials: H
authors.lastname: Ainoedhofer
authors.forename: Geert
authors.initials: G
authors.lastname: Wanten
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Tiemessen
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Gupta
authors.forename: Wouter F J
authors.initials: WF
authors.lastname: Feitz
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Daamen
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Saxena
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
mesh_terms: D000818:Animals; D002417:Cattle; D003094:Collagen / Q000494:pharmacology*; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009852:Omentum / Q000187:drug effects / Q000502:physiology; D011091:Polyesters / Q000494:pharmacology*; D019919:Prosthesis Implantation; D044968:Regenerative Medicine / Q000379:methods*; D012756:Sheep; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D011091:Polyesters; C016240:polycaprolactone; D003094:Collagen